Tyrosine kinase inhibitors (TKIs) are the standard of care for non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation. The efficacy of TKIs and prognosis of EGFR-mutated patients with compound EGFR mutation, oncogene mutation, suppresser gene mutation or other diver gene mutation are worse than those of patients with a single EGFR mutation. This article makes a review of related clinical researches aiming to provide references for clinical scenarios. To sum up, molecular alterations and clinical features should be correlated as accurately and dynamically as possible in the diagnostic and therapeutic process, and combined therapeutic strategies should be chosen flexibly and reasonably to improve patients’ survival and prognosis.
Objective To study the clinicopathologic features which influence the prognosis of patients with stage Ib nonsmall cell lung cancer (NSCLC) after operation, and discuss the indication of postoperative chemotherapy. Methods From January 2002 to December 2002, the clinical materials of 152 patients who underwent complete pulmonary lobectomy and were confirmed to have stage Ib NSCLC by postoperative histopathological examination were collected from Shanghai Chest Hospital. There were 82 male and 70 female cases aged from 33-80 years. The mean age was 63.0 years. KaplanMeier method was used to compare and analyze the age, gender, tumor diameter, tumor location, lymphatic or vascular carcinoma embolus, differentiation, pleural invasion and chemotherapy of patients. Cox regression model was used to do prognostic multivariate analysis to above factors. Results The 5year survival rate was 71.1%. The median survival time was 44.20 months. The results of single factor analysis showed that the tumor diameter was longer than 5 cm（χ2=4.020，P=0.042）, lymphatic or vascular carcinoma embolus existed（χ2=14670，P=0.001）, poorly differentiated tumor（χ2=8.395，P=0.004）, and those whose tumors were located on middlelower lobars had a poor prognosis（χ2=3.980，P=0.045）. The age(χ2=0.478，P=0.740), gender(χ2=0.571，P=0.450), pathological type(χ2=0.406，P=0.816), pleural invasion(χ2=0.022，P=0.882) and postoperative chemotherapy of patients (χ2=1.067，P=0.302)had no relationship with postoperative survival. The results of multivariate analysis showed that lymphatic or vascular carcinoma embolus（P=0.006，95%CI:1.491,10.524） and poorly differentiated tumor（P= 0.001,95%CI:0.116,0.578） were the main factors which influenced the survival rate of patients. Conclusion The tumor differentiation and lymphatic or vessel carcinoma embolus of patients with stage Ib NSCLC are important factors which influence prognosis and survival rate. The poorly differentiated tumor and lymphatic or vessel carcinoma embolus could be regarded as one of the indications of postoperative chemotherapy.
ObjectiveTo study the effect of Tangeretin on non-small cell lung cancer (NSCLC) and the tumor stemness, and to find the molecular mechanism of its effect. MethodsWe used cell counting and cell cloning experiments to study the effect of Tangeretin on the proliferation of NSCLC cells in vitro. The effect of Tangeretin on the invasion of NSCLC cells was detected by transwell assay. We detected the effect of Tangeretin on the proliferation of NSCLC cells in vivo by nude mouse tumor-bearing experiment. The effect of Tangeretin on tumor stemness of NSCLC cells was detected by self-renew assay, and CD133 and Nanog protein expressions. The expressions of PI3K/AKT/mTOR signaling pathway-related proteins were detected by Western blotting (WB). ResultsTangeretin had a good inhibitory effect on the proliferation of NSCLC cells in vivo and in vitro. Cell counting experiment, clonal formation experiment and nude mouse tumor-bearing experiment showed that Tangeretin could inhibit the proliferation activity, clonal formation ability, and tumor size of NSCLC cells in vivo. Self-renew experiments showed that Tangeretin could inhibit the self-renew ability of NSCLC cells. WB experiments showed that Tangeretin inhibited the expressions of tumor stemness markers CD133 and Nanog in NSCLC cells. Tangeretin could inhibit the activation of PI3K/AKT/mTOR signaling pathway-related proteins in NSCLC cells, and the activation of PI3K/AKT/mTOR signaling pathway could partially remit the inhibitory effect of Tangeretin on tumor stemness of NSCLC cells. ConclusionTangeretin can inhibit the tumor stemness of NSCLC cells, which may be related to the regulation of PI3K/AKT/mTOR signaling pathway.
Lobectomy is the standard surgical procedure of non-small cell lung cancer (NSCLC). Based on parenchymal-sparing advantage, better postoperative lung function, rapid recovery and less invasiveness, segmentectomy has been widely used in early peripheral non-small cell carcinoma in recent years. But there was no randomized clinical trials confirming survival benefit of segmentectomy. Led by Asamura, the Japanese Clinical Oncology Group (JCOG) has conducted a series of studies on this topic. Ever since the presentation at the 101st Annual Meeting of the American Society of Thoracic Surgeons (AATS) in 2021, the results of JCOG0802/WJOG4607l have triggered massive debate. This study was aimed at determining whether segmentectomy was non-inferior to lobectomy in overall survival in patients with early peripheral NSCLC (tumor diameter≤2 cm and consolidation tumor ratio>0.5), and the results were published in The Lancet on 22 April 2022. The 5-year overall survival rate was higher in the segmentectomy group than that in the lobectomy group, despite a higher rate of local recurrence, suggesting that segmentectomy should be the standard surgical procedure for those patients. Results of this study provide high-level evidence-based medicine evidence for the safety and effectiveness of segmentectomy, and are expected to promote the application of segmentectomy in those patients or even more other patient populations. However, due to the increased local recurrence rate and unsatisfactory postoperative lung function, there are still problems to be solved to make segmentectomy a standard surgical procedure. This paper interprets this study, discusses its instructiveness in clinical practice and summarizes its limitations.
ObjectiveTo systematically review the efficacy and safety of crizotinib in the treatment of non-small cell lung cancer (NSCLC).MethodWe electronically searched databases including the Cochrane Library (Issue 5, 2017), PubMed, Embase, China Biology Medicine Database, China National Knowledge Internet Database, VIP Database and Wangfang Data from the establishment to May 2017. The randomized controlled trials (RCTs), non-RCTs, case series and case reports on crizotinib for NSCLC were included. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, assessed the methodological quality of included studies, then make Meta-analysis and descriptive analysis.ResultA total of 15 studies were included, including 4 RCTs, 1 non-RCT, 4 case series and 6 case reports. The results indicated that the progression-free survival time of crizotinib group was 8 months, which was better than chemotherapy group (4.6 months). The results of Meta-analysis showed that the response rate in the crizotinib group was higher than that in the chemotherapy group [RR=2.35, 95%CI (1.59, 3.46), P<0.000 1]. The one year survival rate in the crizotinib group was 74.5%-78.6%. The incidences of adverse reactions including dysopsia, dysgeusia, diarrhea, vomiting, constipation, transaminase lifts, upper respiratory tract infection, edema and dizziness in the crizotinib group were higher than those in the chemotherapy group (P<0.05), while the incidences of adverse reactions including leukopenia, thrombocytopenia, alopecia and fatigue in crizotinib group were lower than those in the chemotherapy group (P<0.05). Subgroup analysis under precision treatment showed the progression-free survival time of anaplastic lymphoma kinase (ALK)-positive group was 8 months, and it was longer than ALK-negative group of 4 months.ConclusionsBased on current evidence, crizotinib is better than chemotherapy for NSCLC. Due to limited quality of the included studies, the above conclusion needs to be verifed by more high quality studies.
Objective To assess the prevalence of malnutrition in patients with advanced non-small cell lung cancer (NSCLC) using the Global Leadership Initiative on Malnutrition (GLIM) criteria, analyze its associated factors, and explore the adverse effects of malnutrition on advanced NSCLC patients in multiple aspects. Methods Patients with NSCLC who were hospitalized for the first time in the Department of Oncology, Shangjin Hospital, West China Hospital, Sichuan University between January and December 2021 were retrospectively selected as the study objects. Malnutrition assessment was carried out in all patients according to GLIM criteria, and the current situation and related factors of malnutrition were analyzed. The Barthel index scale was used to compare the daily activity ability between the malnourished group and the non-malnourished group, the Quality-of-Life Questionnaire-Core 30 scale was used to compare the quality of life between the two groups, and the adverse reactions of the two groups were compared by the hospital information system course records. Results According to GLIM diagnostic criteria, 134 of 285 patients (47.0%) were diagnosed with malnutrition. The results of binary multiple logistic regression analysis showed that age [60-69 vs. <60 years old: odds ratio (OR)=2.323, 95% confidence interval (CI) (1.277, 4.397); ≥70 vs. <60 years old: OR=10.816, 95%CI (4.185, 27.959)], previous medical history [OR=2.740, 95%CI (1.313, 5.717)], and albumin level [OR=0.905, 95%CI (0.848, 0.965)] were associated with malnutrition in patients with advanced NSCLC (P<0.05). The daily activity ability and quality of life in the malnourished group were significantly worse than those in the non-malnourished group (87.57±12.48 vs. 91.82±6.77, P<0.05; 76.22±11.52 vs. 83.96±9.75, P<0.05), and the incidence of adverse reactions in the malnourished group was higher than that of the non-malnourished group (50.7% vs. 31.8%, P<0.05). Conclusions The prevalence of malnutrition in patients with advanced NSCLC is high, and advanced age, previous medical history and albumin are related factors of malnutrition in patients with advanced NSCLC. Combined malnutrition may have adverse effects on mobility, quality of life and adverse effects of anti-tumor therapy in advanced NSCLC patients.
ObjectiveTo summarize our initial experience in robot-assisted left upper lobectomy for non-small cell lung cancer. MethodsFour patients with non-small cell lung cancer underwent robot-assisted left upper lobectomy with da Vinci S surgical system (Intuitive Surgical, California) in General Hospital of Shenyang Military Area Command between March and August 2013. There were 3 male and 1 female patients, and their age was 58.8 years (range:49-67 years). We used general anesthesia with double lumens trachea cannula. The patients set in right lateral decubitus position with jackknife. We used 3 arms of the robot system. A single direction lobectomy procedure or an anatomic lobectomy procedure was used according to the differentiation of fissure. Systemic lymph node dissection was performed for all patients. ResultsFour patients with left upper lobectomy were completed with total robotic procedure without conversion. Postoperative pathological examination showed all the patients were of all adenocarcinoma with 2 patients inⅠA stage and 2 patients inⅢA stage. The range of operating time was 100-150 min, intraoperative blood loss was 30-80 ml and no blood transfusion was needed for the patients. The drainage time was 6-20 days. All of the 4 patients were discharged smoothly. The patients were followed up for 10-15 months without recurrence or metastasis. ConclusionRobot-assisted left upper lobectomy is safe and feasible for non-small cell lung cancer.
Objectives To evaluate the clinical effectiveness and safety of combined induction therapy of interferon (IFN) with chemotherapy for survival of the patients with advanced non-small cell lung cancer (NSCLC) by meta-analysis. Methods All clinical trials of addition of IFN plus chemotherapy versus chemotherapy alone for induction therapy to advanced NSCLC patients in MEDLINE (1966-2006), EMBASE (1984-2006.1) and The Cochrane Library (Issue 1,2006) were identified. The references of related studies and Education Books of ASCO and ESMO meeting were handsearched. The quality of included trials was evaluated. Data were extracted by two reviewers independently with a designed extraction form. RevMan 4.2.7 software was used for data analysis. Results Five randomized controlled trials involving 360 patients were included. The pooled result of 3 studies showed that IFN plus chemotherapy induction treatment did not improve 1-year survival rate with RR 0.76, 95%CI 0.46 to 1.26. The pooled result of 5 studies showed that IFN plus chemotherapy induction treatment did not improve response rate with RR 1.40, (0.83 2.34). The pooled result showed that IFN plus chemotherapy induction treatment might significantly increase leukopenia and thrombocytopenia with RR 2.61,95%CI1.70 to 3.99) and RR 4.78,95%CI 1.87 to 12.19 respectively . Conclusion Insufficient data exists to state whether IFN plus chemotherapy induction treatment can improve 1-year survival rate and response rate. IFN plus chemotherapy may increase occurrence of leucopenia and thrombocytopenia. Further studies are warranted.
Based on new clinical evidence, the National Comprehensive Cancer Network (NCCN) annually updates and releases the "NCCN Guidelines for the Clinical Diagnosis and Treatment of Non-Small Cell Lung Cancer" which has become the reference for clinical diagnosis and treatment approved and complied by clinicians worldwide. On November 25, 2020, the latest 2021 V1 version of "NCCN Clinical Diagnosis and Treatment Guidelines for Non-Small Cell Lung Cancer" (hereinafter referred to as "Guidelines") was released. Compared with the 8th edition of the "Guidelines" in 2020, many updates focused on the progress of targeted and immunotherapy. This article will provide the interpretations of the updated therapy content of this edition of the guidelines.
ObjectiveTo reveal the potential mechanism of cisplatin resistance in non-small cell lung cancer A549 cells by comparing the expression profiles of wild-type A549 cells and cisplatin-resistant A549 cells (A549/DPP) through whole transcriptome sequencing analysis.MethodsThe cisplatin resistant A549 (A549/DDP) cell line was first established. Then, the whole-transcriptome analysis was conducted both on A549 and A549/DDP cells. Next, the differentially expressed RNAs of lncRNA-seq, circRNA-seq, and miRNA-seq data were identified, respectively, followed by functional enrichment analysis. Finally, a comprehensive analysis based on the whole transcriptome data was performed and the construction of the ceRNA network was carried out.ResultsA total of 4 517 lncRNA, 123 circRNA, and 145 miRNA were differentially expressed in A549/DDP cells compared with the A549 cell line. These different RNAs were significantly enriched in cancer-related pathways. The ceRNA network contained 12 miRNAs, 4 circRNAs, 23 lncRNAs, and 9 mRNA nodes, of which hsa-miR-125a-5p and hsa-miR-125b-5p were important miRNAs based on the topological analysis.ConclusionTumor necrosis factor signaling pathway and p53 signaling pathway are involved in A549/DPP resistance. Hsa-miR-125a-5p and hsa-miR-125b-5p may be potential targets for reversing cisplatin resistance.